Hypersensitivity Type III- Hunter Flashcards
What is type III hypersensitivity driven by?
IgG, immune complexes, complements and phagocytes
What is an example of a type III hypersensitivity response?
serum sickness, systemic lupus erythematosus
What can cause immune complex diseases?
microbial antigens
drugs and biologics
molds, spores, chemicals
self antigens
What determines the pathology of a type III hypersensitivity reaction?
dose and route
What will a high dose intravenously of an antigen cause?
vasculitis
nephritis
arthritis
What will a subcutaneous dose of an antigen cause?
arthus reaction
What will an inhaled dose of an antigen cause?
farmer’s lung
What is an arthrus reaction?
a local type III hypersensitivity reaction
What kind of immune complex problem is this:
with microbial antigens such as streptococcal infections, malaria, and viral hepatitis can overwhelm the system that rids the body of immune complexes leading to deposition of excess immune complexes into blood vessels and tissues.
persistent infection
What kind of immune complex problem is this:
drugs and biologics form acute immune complex disease which can lead to the arthus reaction and serum sickness
injected antigen
What kind of immune complex problem is:
molds, spores and chemical and lead to immune complexes and hypersensitivity pneumonitis (extrinsic allergic alveolitis) this:
inhaled antigen
What kind of immune complex problem is this:
self-antigens are bound by antibodies forming complexes and lead to chronic disease like that seen in systemic lupus erythematosis, and rheumatoid arthritis
autoimmunity
How do you clear an immune complex?
The C3b/C4b found on immune complexes will bind CR1 on RBCs and be taken to the liver or spleen to be cleared.
What does the C3b/C4b on immune complexes bind to on the RBC?
CR1
What destroys immune complexes in the spleen?
splenic macrophages
What destroys immune complexes in the liver?
kupffer cells
What do kupffer cells and splenic macrophages have on them to allow them to bind and destroy immune complexes?
FC receptors
Do the RBCs attached to the immune complexes get destroyed as well?
no they are safe and return to the circulation.
(blank) factors influence immune complex deposition.
hemodynamic
Deposition of immune complexes in blood vessel walls leads to (blank)
immunopathology
Where do immune complexes deposit in the vasculature?
in between endothelial cells
When immune complexes deposit in the vasculature, what is activated?
complement releasing anaphylatoxins (C5a and C3a)
So once a immune complex deposits in between endothelial cells and anaphylatoxin (C5a and C3a) are activatd what happens next?
neutrophils are recruited to the site and bind immune complexes by their Fc receptors and become activated. The neutrophils attempt to phagocytize the complex but cant so they release a bunch of granules, inflammatory mediators, and enzymes to cause tissue destruction.
What is the most common post-infectious actue proliferative nephritis?
post-streptococcal glomerulonephritis
Patients with post-streptococcal glomerulonephritis present with what 2 things?
hematuria and proteinuria
WHen you see a lumpy bumpy glomerulus, what should you be thinking?
deposition of complement
How can you induce the arthus reaction?
locally inject antigen in an immune individual w/ lots of pre-existing IgG antibody to the antigen-> local immune complex formation-> activation of FcgammaR3 on mast cells induces their degranulation-> local inflammation, increased fluid and protein release, phagocytosis and blood vessel occlusion
Local injection of antigen in individuals with high levels of pre-existing antibodies can cause the (blank) reaction
arthus reaction
FCepsionRI receptors on mast cells, basophils, activated eosinophils have this receptor to do what?
to release their stuff in response to IgE!!!!
FCgammaRIII receptors on mast cells respond to what and do what?
IgG immune complexes and degranulate
(blank) form in the setting of high local concentration of vaccine antigens and high circulating antibody concentrations.
immune complexes
A local vasculitis is associated with deposition of (blank) and (blank)
immune complexes and complement activation
What are these symptoms of:
severe pain, swelling, induration, edema, hemorrhage, and occasionally necrosis.
arthrus reaction
when does an arthrus reaction typically occur after a vaccine?
4-12 hours after vaccination
What is the mechanism behind penicillin-induced serum sickness?
the chemically reactive penicilloyl moiety binds to self proteins and induces an antibody response, IgG anti-peniciliin antibodies form immune complexes with penicilin-> complement activation releases C3a which causes hitamine release from mast cell and urticaria (hives).
What is extrinsic allergic alveolitis (hypersensitivity pneumonitis)?
immune complexes with inhaled fungal antigens (farmer’s lung-bird fancier’s disease)
What involves the development of IgG antibodies to inhaled mold that form immune complexes?
Extrinsic allergic alveoitis
Why are immune complexes so sucky?
because they fix complement and release anaphylatoxns causes local inflammation.
Acute exacerbations of extrinsc allergic alveolitis can be treated by what?
corticosteroids
What is type IV hypersensitivity (delayed type hypersensitivity) caused by?
Th17 cells, Th1 cells, Th2 cells
The Th1 delayed type hypersensitivity (DTH) response is orchestrated by (blank) produced by macrophages; T cells make IFN-gamma that further activates (blank)
IL-12
macrophages
The TH17 delayed hypersensitivity reaction is driven by (blank) and (blank) produced by macrophages. T cells make (blank) and (blank) that recruit and activate neutrophils
IL-23 and TGF-beta
IL-17 and IL-22
WHat does IL-17 and IL-22 do?
recruit and activate neutrophils
What is the TH17 DHT reaction driven by?
IL-23 and TGF-beta
The (blank) response involves cytoxocity and is a component of several autoimmune diseases like Type I diabetes
CD8 DTH response
CD8 makes what cytokine?
IFN-gamma
So describe the whole type IV hypersensitivity (delayed type hypersensitivity) response?
IL-12 released from macrophages makes Th1 which releases IFN gamma and TNG that further activates macrophages
THEN
IL-23 and TGF-beta produced by macrphages triggers T cells to make IL-17 and IL-22 that recruit and activates neutrophils
THEN
CD8s release IFN gamma and kill shit
Why do you get the wheel and flare when you get a TB shot?
Antigen is injectin into subcutaneous tissue and the antigen is processed by APCs and then TH1 cells recognized the antigen and release cytokines onto vascular endothelium which will recruit phagocytes and plasma to site of antigen injection and causes visible lesion
T cell-mediated reactions are called DTH because they take (blank) hours to mature
24-72 hours
What is allergic contact dermitis caused by?
CD4 or CD8 T cells
Explain how allergic contact dermatitis is caused
small highly reactive molecules penetrate skins-> create haptens-> haptens are presented by MHC molecules-> Langerhan dendritic cells take up and process antigen, these migrate to lymph nodes and activate T cells.-> The memory T cells migrate to the dermis->Then an approximate exposure triggers memory T cells which release IFN-gamma. IFN-gamma sitmulates keratinocytes to release cytokines and chemokines that enhance inflammatory rsponse by recruiting and activating monocytes
In allergic contact dermatitis, what does IFN-gamma stimulate?
Keratinocytes to release cytokine and chemokines
In type IV hypersensitivity to a contact sensitiizing agent
Hapten binds self protein in the skin and is pinocytosed by (blank) and are present in (bank) molecules to (blank) cells
dendritic cells
MHC class II
CD4 T cells
In type IV hypersensitivity to a contact sensitiizing agent, previously sensitized (Blank) cells interact with langerhan dendritic cells
T cell
In type IV hypersensitivity to a contact sensitiizing agent, (bank) stimulates keratinocyes to make cytokines and chemokines.
IFN-gamma
In type IV hypersensitivity to a contact sensitiizing agent, IFN-gamma stimulates keratinocytes to make cytokines and chemokines which wil attract what cels to the site?
mononuclear cells
What happens upon second exposure of poison ivy?
How do you treat it?
severe reaction triggered by memory T cells result in contact dermatitis and epidermal blisters with dermal and epidermal mononuclear infiltrates.
systemic corticosteroids
Explain nickel dermatitis
chemically reactive metals like nickle bind to host proteins and activate T cells-> T cels release IFN-gamma which activate keratinocytes-> active keratinocytes release mediates that cause mononuclear infiltrate of dermis.
What kind of hypersensitivity is acrylate and latex?
Type IV hypersensitivity
What does IFn gamma really do?
brings in macrophages.
